Materials and Methods: HMGB1 expression by cultured human PDL-cells and of orthodontically treated rats was analyzed by means of immunocytochemistry/ELISA. The influence of HMGB1 secreted PDL-cells on macrophage physiology was investigated by migration and osteoclastic differentiation assays. To examine the effect of HMGB1 on PDL-cell differentiation, cells were exposed to HMGB1 and analyzed for cell differentiation capacity towards an osteogenic phenotype at the transcriptional/translational level. Furthermore, HMGB1 was studied for its capacity to modify PDL-cell migration and proliferation.
Results: Induction of mechanical stress in vivo and in vitroresulted in enhanced HMGB1 protein expression and an intracellular translocation of HMGB1 in the initial phase of tissue repair. Exposure of human macrophages to HMGB1 influenced migration and osteoclastic differentiation only in combination with other proinflammatory mediators. Supplementation of PDL-cell cultures with HMGB1 induced the expression of osteogenic markers, PDL-cell migration and proliferation.
Conclusions: These data clearly point to the dual role of HMGB1 in periodontal tissue repair with an immune modulatory function when acting in concert with other cytokines in the initial phase of tissue remodeling, as opposed to delivering important anabolic functions on PDL-cells in the phase of periodontal reconstruction. These findings extend the basis for possible prevention and therapeutical intervention strategies for tissue damage that might occur in the course of orthodontic treatment.